Update on Occupational Exposure

The following is updated information on the current status of occupationally acquired HIV infection primarily based on data from the Centers for Disease Control and Prevention.

Reported Cases

The number of reported cases through June, 1995 was 46 confirmed cases and 97 possible cases. Confirmed cases require the demonstration of seroconversion in the context of a CDC-defined exposure. Possible cases are those in which acquisition of infection is the workplace is suspected, but seroconversion was not demonstrated. The current rate of reports for documented cases is approximately 6/year and for possible cases is approximately 12/year. Among the documented cases, the following occupations apply: laboratory technicians--18, nurses--16, nonsurgical physicians--6, surgical technician--2, dialysis technician--1, respiratory therapist--1, maintenance worker--1 and health aide--1. There have been no surgeons in the confirmed case category, but 4 in the "possible" category. In terms of the type of exposure, 4 of the 46 cases involved mucocutaneous surface exposure. All exposures in the documented category have involved exposure to blood or bloody body fluid except for 3 which involved work with high concentrations of the virus in culture and one where the source of the virus was not defined.

Risk

Multiple studies have defined the efficiency of transmission with a needlestick injury from a HIV-infected source to be 0.25-0.3% or approximately 1/3,000 (Ann Intern Med 118:98, 1993). The risk with mucocutaneous exposure is confirmed with 4 anecdotal but well-confirmed cases; prospective studies have failed to identify any cases in approximately 1,000 mucocutaneous exposures.

The CDC has completed a retrospective case-control study of health care workers with documented occupational percutaneous HIV exposures from 1/88 to 8/94. This included 31 HCWs with seroconversion and 679 control from 191 medical care facilities. The results showed the following odds-ratios favoring HIV transmission (MMWR 44:929, 1995):

Deep injury	16.1
Visible blood on device	5.2
Procedure involving needle placement in vein or artery	5.1
Terminal illness in source	8.4
AZT prophylaxis	0.2

The conclusion is that risk of HIV transmission depends on two obvious variables and one surprise: The obvious were the quantity of blood (as indicated by depth of injury, visibility of blood on device and procedure done) and advanced HIV disease in the source patient (reflecting higher viral burden). The surprise is the benefit with use of AZT prophylaxis. In controlling for other factors, the analysis showed the risk with AZT use was reduced by 79% (MMWR 44:929, 1995).

AZT Prophylaxis

The case controlled study by the CDC showed a statistically significant benefit for those who received AZT with an odds ratio of 5:1. The implication is that AZT reduces the risk of transmission by 5-fold. there has been cautious interpretation of these results since the study was not a prospective, blinded trial; nevertheless, the results were striking.

AZT protocol (CDC, San Francisco General Hospital, Clinical Research Center, NIH):

1. Must be started within 72 hours of exposure.
2. Female HCW of childbearing potential must have negative pregnancy test and agree to avoid pregnancy and breast feeding until 4 weeks after AZT therapy.
3. Dose: 200 mg po q4h x 72 hours, then 100-200 mg po q4h x 25 days. (We usually give a 72 hours "starter pack" to initiate prophylaxis as quickly as possible while the HCW reviews options).
4. Laboratory monitoring: CBC and chemistry panel at 2, 4, and 6 weeks. HIV serology at 0, 6, 12 and 26 weeks; also at one year if AZT prophylaxis is elected due to possible delay in seroconversion.

Future Options

Interest in promoting better prophylaxis strategies have focused on the time to initiation of antiretroviral prophylaxis and use of more potent regiments. With regard to regimens, many have expressed interest in the use of AZT combined with 3TC or a protease inhibitor. Of particular interest is the use of alternative agents when the source has received prolonged therapy with AZT thus increasing the likelihood of AZT resistance. On theoretical problem with nucleoside analogs (AZT, ddI, ddC, 3TC and d4T) is that these drugs require activation which delays the time of onset of antiviral activity. Protease inhibitors also require activation in vivo. Non-nucleoside RT inhibitors, such as nevirapine, don't require activation, are potent against HIV and have no resistance in "community strains." It should be noted that there is no clinical experience to support any of these regimens other than AZT monotherapy, and even the data with AZT is based on retrospective evaluation of an uncontrolled experience. Finally, the most promising potential development concerns PMPA which proved to be universally successful in protecting Macaques when started up to 24 hours after SIV challenge (Science 1995; 270: 1197). This drug is a nucleoside analog that is already activated and can enter both infected and uninfected cells.

Guidelines

The CDC issues the last guidelines on management of HIV exposures in the workplace in 1990 (MMWR 39:RR-1, 1990). These are badly outdated, especially with respect to the AZT issue. This document will be re-written as a result of a CDC sponsored meeting that took place March 3-4, 1996.